KLHL31 (kelch-like family member 31) is a BTB/POZ domain-containing protein that functions as a transcriptional repressor in muscle and cardiac tissues 1. The protein inhibits transcriptional activities of both TPA-response elements (TRE) and serum response elements (SRE) through its N-terminal BTB domain, which serves as the primary region responsible for transcriptional repression 1. KLHL31 suppresses MAPK/JNK signaling by reducing JNK activation and decreasing phosphorylation of the JNK target c-Jun 1. Beyond JNK signaling, KLHL31 modulates canonical Wnt/β-catenin signaling and plays a critical role in embryonic skeletal myogenesis by promoting cell cycle withdrawal and differentiation 2. The protein localizes to both nucleus and cytoplasm in cultured cells, though predominantly cytoplasmic in primary cardiomyocytes 1. KLHL31 likely functions as a component of Cullin-E3 ubiquitin ligase complexes that target tissue-specific proteins for degradation 3. Clinically, KLHL31 has been identified as an effector gene in exercise-induced cardiac protection and rejuvenation 4, and genetic variants in KLHL31 associate with leptin concentration regulation and early-onset adiposity 5. Its expression is tightly controlled by tissue-specific epigenetic mechanisms including enhancer chr6 and DNA hypomethylation 3.